A regenerative stem cell phenotype marked by ANXA1 defines aggressive colorectal cancer biology

Relative ANXA1 enrichment in colorectal cancer is linked to aggressive, stroma-rich biology and poor prognosis, with ANXA1 dominance independently predicting recurrence (HR 1.43, 95% CI 1.08–1.90).

• Why it matters: LGR5 and ANXA1 mark distinct intestinal stem cell states, but their clinical meaning in colorectal cancer—especially across molecular subtypes, immune context, and patient outcomes—remains unclear.
• What they did: Dual-colour in situ hybridisation quantified ANXA1 and LGR5 on tissue microarrays from 2163 SCOT trial patients, then related marker-positive area to imCMS, immune features, and survival using Kaplan–Meier and multivariable Cox models.
• The result: ANXA1 and LGR5 were inversely enriched across parameters, with ANXA1 highest in CMS1 and LGR5 highest in CMS2; combining both markers improved cancer-specific survival (p<0.001) and recurrence-free interval (p=0.004).

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